Longitudinal studies have identified clinical characteristics associated with an increased risk for alcohol and drug abuse in adolescents and young adults. Factors such as persistent patterns of impulsive behaviors in childhood appear to play an important role in the development of addiction. Although available evidence suggests that alterations in the functioning of reward and regulatory control networks are likely to mediate vulnerabilities for addiction, the nature of the neural mechanisms preceding the impact of substance use are largely unknown. Animal and human imaging studies have indicated that sensitivity to reward may be influenced by impulsive decision making, suggesting a possible neurophysiologic link between circuits associated with deficits in response inhibition and sensitivity to reward. Better understanding the relationship between these two systems before exposure to substances is an important initial step in refining our knowledge of the neurobiological basis of addiction, and may provide useful insights regarding the development of new psychosocial and psychopharmacologic preventive interventions targeted at decreasing risk. We are in excellent position to use functional magnetic resonance imaging (fMRI) to study patterns of activation in brain areas associated with reward circuitry and regulatory control networks associated with impulsive behavior, and to study the contribution of these neural systems to the pathophysiology of addiction in at risk pre-adolescents before the development of substance abuse. The current project will test the hypothesis that a deficit in inhibitory control underlies high risk status, using a newly validated fMRI task which tests reward sensitivity and cognitive conflict. We propose to perform these scans in 24 children ages 10-13, divided in 2 groups: i) subjects with no family history of SUD who are clinically impulsive and who have a measured deficit in inhibitory control, and ii) age and gender matched normal controls. This study offers a unique opportunity to delineate the role of reward and regulatory control networks in youth in mediating risk for SUD. PUBLIC HEALTH RELEVANCE: The primary goals of this proposal are to provide new data in the areas of neurobiology of adolescent substance use disorder (SUD) and the questions of particular relevance are: i) whether impulsive youth differ in their risk for future substance abuse compared to normal children , and ii) how the brain activity in areas known as the reward and executive control system differ between highly impulsive vs. non-impulsive children. Identifying potential baseline differences in these systems will contribute to a better understanding of the neurobiological underpinnings of addiction and will provide information about potential targets for the development of novel biological treatments. In addition, it will establish a base for further investigations of the changes that occur in these systems both as result of normal development and environmental impacts (e.g. drugs of abuse) and may inform researchers and clinicians about specific developmental windows for prophylactic and therapeutic interventions.